Leishmania

Question 1

Where is Leishmania found?

Answer 1

historically Mediterranean basin and Portugal , reports in France, Germany, Switzerland, and the Netherlands; southern US (TX, OK, AL, OH, MI); endemic Central and South America; Dz may occur months to years after infection so can be seen anywhere

Question 2

What is the vector for Leishmaniasis?

Answer 2

Sandflies: Phlebotomus in new world, Lutzomyia in old world

Question 3

When is Leishmaniasis most common?

Answer 3

Frequency of infection increases in warm months when vector load is high

Question 4

What is the reservoir for Leishmania?

Answer 4

Domestic and wild dogs, rodents, other wild mammals

Question 5

In general, what is the cause of tissue damage in leishmaniasis?

Answer 5

Granulomatous inflammation and immune complex deposition, inflammatory and ulcerative lesions at pressure points (may develop cutaneous lesions at sites of external trauma, and resultant inflammatory processes, and amastigotes in blood cells transported to inflamed areas)

Question 6

What is the incubation period for Leishmania?

Answer 6

Weeks to several years, most dogs young <3 or older 8-10, GSD and Boxers increased risk as well as dogs that are outdoors overnight, 10-50% of seropositive dogs are not clinical and remain healthy for prolonged periods if not permanently; NA Foxhounds 1980-2001

Question 7

What is the most common presentation for Leishmaniasis in dogs?

Answer 7

Exfoliative dermatitis. Cutaneous lesions in 80% of dogs w/ visceral dz. Exfoliation (silvery white asbestos like scaling) can be generalized but typically most pronounced on head, pinnae, and extremities.

Question 8

Describe common skin lesions seen in Leishmania.

Answer 8

80% of dogs w/ visceral dz. Exfoliation (silvery white asbestos like scaling) can be generalized but typically most pronounced on head, pinnae, and extremities; also nasodigital hyperkeratosis, hypotrichotic or alopecic skin, periocualr alopecia; 2nd most common is ulcerative dermatitis; others are onychogryposis, paronychia, sterile pustular dermatitis, nasal depigmentation with erosion and ulceration, and nodular dermatitis; secondary pyoderma in 25% of cases, generalized demodicosis due to Leishmania-induced cell-mediated immunodeficiency

Question 9

What are signs of systemic disease with Leishmania?

Answer 9

Varied. >50% have decreased endurance, weight loss, somnolence; common generalized lymphadenopathy and hepatosplenomegaly; others muscle wasting, cachexia, intermittent fever, keratoconjunctivitis, epistaxis, and lameness; PU/PD and other signs of progressive renal failure

Question 10

Can cats get Leishmania?

Answer 10

They are resistant to experimental infection and spontaneous cases are rare; majority of cases are nodular or crusting dermatitis of the lips, nose, eyelids, and pinnae or paws; generalized exfoliative dermatitis can also be seen

Question 11

What is endemic visceral Leishmaniasis?

Answer 11

NA Foxhounds, many dogs asymptomatic but others had chronic wasting, conjunctivitis, anterior uveitis, retinitis, facial alopecia, lymphadenopathy, polyarthritis, muscle atrophy and protein-losing nephropathy/renal failure

Question 12

What is the immunologic response to Leishmaniasis?

Answer 12

Resistance= stimulation of Th1 response, Susceptibility= Th2 response; IL-2 and TNFa are protective; with infection IgG, IgM, IgA, and circulating immune complexes increase and, with high titer, predispose to renal dz; with infection numbers of CD21+, CD4+, CD5+, and CD8+ cells decrease and degree of incompetence influences the severity of clinical signs; with a persistent cell-mediated response the dogs clinical signs are absent or milder, and number of organisms in tissues is fewer

Question 13

What are differentials for Leishmania in dogs?

Answer 13

PF
SLE
Zinc-responsive dermatosis
Necrolytic migratory erythema
Sebaceous adenines
Lymphoma

Question 14

What are laboratory findings with Leishmaniasis?

Answer 14

Nonregenerative anemia, hyperglobulinemia, hypoalbuminemia, proteinuria; tests for IM dz can be positive (ANA, Coombs, LE cell prep, rheumatoid factor); can find the tissue on cytologic or histopathologic tissue, PCR assays, cultures, xenodiagnosis, or demonstration of anti-Leishmania Ab or positive skin test reaction; dogs can have seropositivity with absence of dz but spontaneous elimination of the parasite is rare therefore positive likely indicates infection

Question 15

Is Leishmania intracellular or extracellular?

Answer 15

Intracellular and extracellular, found in 50% of cases on histology: round to oval, 2-4um with round basophilic nucleus and small rod-like kinetoplast; Amastigotes found in macrophages in affected tissues (papular, nodular, and ulcerative skin lesions, BM, LN, spleen and Buffy coat smears of peripheral blood); Amastigotes easiest to ID with Giemsa stain and are most often found on smears from LN of dogs with lymphadenopathy and BM of dogs with anemia; visible in routine stains but best seen with Giemsa or IHC

Question 16

What are the histologic findings with Leishmania?

Answer 16

Organisms hard to find in tissue; lymphoplasmacytic, pyogranulomatous, or granulomatous inflammation with vasculitis; orthokeratotic and parakeratotic hyperkeratosis usually prominent; inflammatory infiltrate predominantly macrophages with fewer numbers of lymphocytes and plasma cells; 9 inflammatory patterns

Question 17

What are the 9 inflammatory patterns seen in Leishmaniasis?

Answer 17

Granulomatous perifolliculitis
Interestitial dermatitis
Superficial and deep perivascular dermatitis
Lichenoid interface dermatitis
Nodular dermatitis
Lobular panniculitis
Suppurative folliculitis
Intraepidermal pustular dermatitis

Question 18

How is Leishmania cultured? Is this clinically useful?

Answer 18

Blood-agar through demonstration of promastigotes, limited availability and long incubation time (30 days) limit the use

Question 19

What test has the most specificity and is useful for monitoring response to treatment?

Answer 19

quantitative rt-PCR; samples most likely to be positive (highest to lowest sensitivity): BM and LN, skin, conjunctiva, Buffy coat, and whole peripheral blood; fresh or frozen more likely to be positive than formalin-fixed tissues

Question 20

What is Xenodiagnosis?

Answer 20

The process of allowing laboratory-bred phlebotomize vectors to feed on a dog and then examine the flies for the evidence of promastigotes in their gut, highly sensitive and specific but impractical for routine use (Leishmania)

Question 21

What are the serologic tests for Leishmania in dogs?

Answer 21

Time for Ab detection varies from 1-22 months for natural infection; IFAT, ELISA, and ICS available, WHO recommends IFAT; false negatives ~10% regardless of test, false positives secondary to cross-reactivity with Ab to Trypanosoma cruzi, ELISA and ICS Ag tests can differentiate but have lower sensitivity than IFAT; high Ab titers usually present if clinically sick with Leishmania except for rare cases with highly localized lesions or very early infections with clinical signs preceding specific Ab responses

Question 22

Is Leishmania curable?

Answer 22

Considered incurable in vast majority of cases, treatments can bring clinical remission but expect relapses months to years after treatment, probably due to incomplete eradication but cannot could represent reinfection

Question 23

What is the treatment for Leishmania?

Answer 23

Goal is decrease parasite load, treat organ damage, and improve patients immune response against parasite; not licensed but N-methyl-glucamine (meglumine) antimoniate is most common tx in dogs and humans, 100mg/kg SQ SID x 4 weeks, but 50mg/kg BID may be more effective based on pharmacokinetics in dogs; clinical amelioration usually seen in first week, but tx continued for 4 weeks to reduce incidence of relapse; SE include pain at injection site, fever, anorexia, and diarrhea; transient elevations in ALT and Amylase; Tx with meglumine reduces parasite load, increases specific IgG Ab responses, and improves cell-mediated immunologic responses to the parasite

Question 24

What FDA approved treatment can be used for Leishmania?

Answer 24

Allopurinol has some efficacy for Leishmania at 10mg/kg POq12 for 2-24 months, well tolerated and can be combined with meglumine for 6 months for a longer period of clinical remission than with either as single agent

Question 25

What are less common possible treatments for Leishmania?

Answer 25

Aminosidine (also called paromomycin)
Marbofloxacin
Amphotericin B
Miltefosine
Pentamidine
Domperidone
Spiramicin
Metronidazole
Ketoconazole
Brazil has licensed a vaccine